ABSTRACT Cardiac malformations are the most common type of birth defect. Improvements in the management of complex congenital heart disease have resulted in >90% of those born with congenital heart disease now able to survive into early adulthood. In the U.S. alone, there are more adults with congenital heart disease (~1 million individuals) than children. Tetralogy of Fallot (TOF) is the commonest cyanotic congenital heart lesion, and there is now a large and growing population of adults with TOF. The surgical repairs these patients require early in life often lead to residual pulmonary regurgitation that can cause eventual right ventricular enlargement and dysfunction, and pre-dispose to heart failure, arrhythmias, and sudden death. In the course of clinical management, deciding whether and when to perform pulmonary valve replacement to prevent ventricular decompensation is therefore critical and warrants quantifiable means of assessment. The goal of this project is to expand the current Congenital Heart Disease study of the Cardiac Atlas Project database to include a large cohort of patient with post-operative TOF, and to use the patient cardiac magnetic resonance (CMR) exams and other clinical data to derive statistical atlases of shape, biomechanics and electrical dyssynchrony. These atlases will be used to test hypotheses and discover clinical biomarkers that predict outcomes of pulmonary valve replacement based on variations in ventricular shape, mechanical properties and electromechanical dyssynchrony. The specific aims are: (1) To use disease-specific statistical shape atlases derived from non-invasive imaging exams of patients with TOF to test the hypothesis that specific biventricular shape modes can discriminate patients by their degree of recovery of ventricular function and their extent of reverse cardiac remodeling after valve replacement; (2) To use finite element models of biventricular biomechanics to investigate the extent to which clinically significant relationships between ventricular shape modes and improvements in ventricular function post-valve repair are due to shape alone vs. differences in myocardial material properties; and (3) To determine how dyssynchronous electrical activation patterns that give rise to heterogeneous regional contraction affect hemodynamic improvement and reverse ventricular remodeling after pulmonary valve replacement in TOF patients. This work will have a significant impact on the clinical management of congenital heart disease by providing: new insights into biomechanical alterations in post-operative TOF; new predictors of outcomes following pulmonary valve replacement; and a greatly expanded web-accessible database of CMR exams, models and statistical atlases to facilitate clinical research and training in congenital heart disease.